Clinical studies of 5-HT subtype-selective agonists or antagonists have suggested a role of 5-HT in the etiology and treatment of such different neuropsychiatric disorders as the anxiety disorders, depression, alcoholism, schizophrenia, migraine, sexual dysfunctions and Alzheimer's disease (see Murphy, D., Neuropsychiatric Disorders and the Multiple Human Brain Serotonin Receptor Subtypes and Subsystems, Neuropsychopharmacology, 3, No. 5/6, pp. 457-471 (1990). Pharmacological and clinical data suggest that 5-HT and in particular 5-HT.sub.2 receptors may play a role in schizophrenic symptomology and in the mechanism of action of some antipsychotic drugs.
A phenomenon known as prepulse inhibition (PPI) is known to be disrupted in individuals with schizophrenia. PPI is a measure of "sensory gating" or "sensory filtering" in animals and man and disrupted PPI may represent a fundamental deficit in the ability of these individuals to gate sensory information. Studies have shown that the amplitude of the startle reflex is inhibited when the startling stimulus is preceded 30-500 msec by a weak "prepulse". This "prepulse inhibition" (PPI) is a measure of sensorimotor gating that is impaired in disorders characterized by deficient gating of irrelevant sensory information (schizophrenia) or motor activity (Huntington's Disease). Substantial evidence indicates that PPI is modulated by neural circuitry linking the limbic cortex, striatum and pallidum.
It has recently been demonstrated that patients with obsessive-compulsive disorders (OCD) also fail to inhibit or "gate" intrusive, distressing thoughts or images. Since OCD is characterized by deficient "cognitive gating" and by aberrant metabolic activity in circuitry linking the orbital cortex and striatum, it has been predicted that OCD patients might exhibit deficient PPI. Indeed, in a study of eleven OCD patients and 13 normal controls, it was demonstrated that OCD patients exhibited less PPI than control subjects. Swerdlow, N. R., Benbow, C. H., Zisook, S., Geyer, M. A., and Braff, D. L., Impaired Sensorimotor Gating in Obsessive Compulsive Disorder(OCD), abstract from the Abstracts of Panels and Posters, p. 155, American College of Neuropsychopharmacology 31st Annual Meeting, San Juan, Puerto Rico, Dec. 14-18, 1992. These findings suggest that the inability to "gate" intrusive thoughts and images in OCD is accompanied by quantifiable deficits in sensorimotor gating and suggests PPI might be a useful measure for understanding the pathophysiology of OCD. Currently, serotonin-selective reuptake inhibitors (SSRI) are used to treat the symptoms of OCD. However, we are not aware of any data, other than such data as is presented herein, that indicates that SSRIs reverse the deficits in PPI in OCD.